This proposal describes research which will further our understanding of the mechanisms which operate to control the concentration of a specific gene product, glycerol-3-phosphate dehydrogenase, in different cell types. This analysis will include comparison of transcription, GPDH mRNA content, and alternate mRNA processing routes. The structure of the DNA flanking the Gpdh locus will be compared to homologous regions of other genes which share, in part, the tissue localization of GPDH. These genes are glyceraldehyde-3-phosphate dehydrogenase, and Beta hydroxyacid dehydrogenase which will be analyzed during these studies and alcohol dehydrogenase which has been analyzed by others. The point of these comparisons will be to determine of some aspect of DNA structure common to these correlates with the known tissue pattern of gene expression. This set of genes, each of which encodes a pyridine nucleotide linked dehydrogenase, will also be compared in an attempt to elucidate the role of introns during evolution of related games. This class of enzymes are among the most well studied with respect to their physical structure. This has resulted in reasonably precise experimental and theoretical definitions of the functional domains of these proteins. Our studies will compare the positioning of introns in the genes with domain boundaries in each of the proteins. If the hypothesis which has been set forth is correct regarding the role of introns in the evolution of new enzymes we would expect to see some relation between intron positions and domain boundaries in this functionally similar and evolutionarily related set of gene-enzyme systems.